Diurnal beta-endorphin changes in human cerebrospinal fluid

Barreca, T; Siani, C; Franceschini, R.; Francaviglia, Natale; Messina, Valeria; Perria, C; Rolandi, E

doi:10.1016/0024-3205(86)90579-5

Cited by 26 publications

(6 citation statements)

References 12 publications

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“…Given that local sources of the MOR-selective neuropeptide β-endorphin are apparently lacking in CA1 ( Bjorklund and Hokfelt, 1986 ), this raises the question as to why PV-BCs express MORs at all. One possible explanation is that diurnal variation in the levels of brain-wide β-endorphin in the cerebrospinal fluid contribute to the resting excitability and tune the strength of synaptic output via PV-BC MORs, while dynamic, local release of enkephalin in CA1 produces stronger, temporally precise inhibition of cellular output through activation of DORs ( Dent et al, 1981 ; Barreca et al, 1986 ).…”

Section: Discussionmentioning

confidence: 99%

Convergent, functionally independent signaling by mu and delta opioid receptors in hippocampal parvalbumin interneurons

Patel

Weiss

et al. 2021

eLife

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Functional interactions between G protein-coupled receptors are poised to enhance neuronal sensitivity to neuromodulators and therapeutic drugs. Mu and Delta opioid receptors (MORs and DORs) can interact when overexpressed in the same cells, but whether co-expression of endogenous MORs and DORs in neurons leads to functional interactions is unclear. Here, in mice, we show that both MORs and DORs inhibit parvalbumin-expressing basket cells (PV-BCs) in hippocampal CA1 through partially occlusive signaling pathways that terminate on somato-dendritic potassium channels and presynaptic calcium channels. Using photoactivatable opioid neuropeptides, we find that DORs dominate the response to enkephalin in terms of both ligand-sensitivity and kinetics, which may be due to relatively low expression levels of MOR. Opioid-activated potassium channels do not show heterologous desensitization, indicating that MORs and DORs signal independently. In a direct test for heteromeric functional interactions, the DOR antagonist TIPP-Psi does not alter the kinetics or potency of either the potassium channel or synaptic responses to photorelease of the MOR agonist DAMGO. Thus, aside from largely redundant and convergent signaling, MORs and DORs do not functionally interact in PV-BCs in a way that impacts somato-dendritic potassium currents or synaptic transmission. These findings imply that crosstalk between MORs and DORs, either in the form of physical interactions or synergistic intracellular signaling, is not a preordained outcome of co-expression in neurons.

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Section: Discussionmentioning

confidence: 99%

Convergent, functionally independent signaling by mu and delta opioid receptors in hippocampal parvalbumin interneurons

Patel

Weiss

et al. 2021

eLife

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“…These variations appeared to be due to the diversity of methods and experimental conditions involving stress, pain-related manipulations, and infections [111,113,116-118,120,129-133] . Another complicating factor is that β-END levels show diurnal fluctuations in plasma as well as in the CSF [134,135]. The conclusion is that CSF β-END concentration mostly exceeds peripheral β-END, which excludes the possibility that central levels are a passive reflection of peripheral levels.…”

Section: Central and Peripheral β-End Are Regulated Differentiallymentioning

confidence: 99%

Volume transmission of beta-endorphin via the cerebrospinal fluid; a review

Veening

Gerrits

Barendregt

2012

Fluids Barriers CNS

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There is increasing evidence that non-synaptic communication by volume transmission in the flowing CSF plays an important role in neural mechanisms, especially for extending the duration of behavioral effects. In the present review, we explore the mechanisms involved in the behavioral and physiological effects of β-endorphin (β-END), especially those involving the cerebrospinal fluid (CSF), as a message transport system to reach distant brain areas. The major source of β-END are the pro-opio-melano-cortin (POMC) neurons, located in the arcuate hypothalamic nucleus (ARH), bordering the 3rd ventricle. In addition, numerous varicose β-END-immunoreactive fibers are situated close to the ventricular surfaces. In the present paper we surveyed the evidence that volume transmission via the CSF can be considered as an option for messages to reach remote brain areas. Some of the points discussed in the present review are: release mechanisms of β-END, independence of peripheral versus central levels, central β-END migration over considerable distances, behavioral effects of β-END depend on location of ventricular administration, and abundance of mu and delta opioid receptors in the periventricular regions of the brain.

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“…According to the literature, CSF-BE levels are highest early in the morning, between 6 and 9 a.m. [13,103]. In the present thesis, all lumbar puncture on patients were done between 8 and 9 a.m., whereas the timing of lumbar puncture in healthy controls ranged from early morning to very early afternoon.…”

Section: Circadian Variationsmentioning

confidence: 84%

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

Bäckryd¹

2015

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The treatment of both cancer pain and non-cancer chronic pain is still suboptimal. The overall aim of this PhD thesis was to conduct translational pain research at the interface between clinical pain medicine and the field of human proteomics, using the practice of intrathecal analgesia at our institution as a starting point. Hence, the cerebrospinal fluid (CSF) is at the centre of the present dissertation, both as a target for infusing analgesics (Papers I and II – clinical and pharmacological aspects) and as an important biofluid for human biomarker studies (Papers III and IV – proteomic aspects). In Paper I, 28 cases of intrathecal analgesia in cancer patients were prospectively followed. Movement-evoked breakthrough pain remained a major clinical problem throughout the study month despite otherwise successful intrathecal analgesia (defined as good control of spontaneous resting pain paralleled by a marked decrease of concomitant systemic opioid doses). This study therefore illustrates the importance of considering not only spontaneous resting pain but also movement-evoked breakthrough pain. In Paper II, an expert-based algorithm for trialing the intrathecal analgesic ziconotide by bolus injections was evaluated in an open-label study of 23 patients with chronic neuropathic pain. We found few responders (13%) according to the strict criteria of the algorithm, but ziconotide bolus injection trialing seems feasible. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (with very slow tissue penetration due to high hydrophilicity) calls the rationale for ziconotide bolus trialing into question. In Paper III, we found low levels of beta-endorphin in the CSF of chronic neuropathic pain patients (n=15) compared to healthy controls (n=19). We speculate that this might indicate dysfunctional top-down control of nociception. Substance P levels in the CSF did not differ by univariate statistics. In Paper IV, the CSF proteome of 11 patients with chronic neuropathic pain and 11 healthy controls was exploratively studied, combining gel-based proteomics with multivariate data analysis. After eliminating four proteins associated with age, 32 proteins were found to highly discriminate between groups. Among these, the seven proteins having the highest discriminatory power between patients and controls were: one isoform of angiotensinogen, two isoforms of alpha-1-antitrypsin, three isoforms of haptoglobin, and one isoform of pigment epithelium-derived factor. In conclusion, this PhD thesis demonstrates the fruitfulness of studying the CSF, both as a target for infusing analgesics and as a potential mirror of the neurobiological processes involved in pathological pain conditions. The thesis points to the need for more research into the mechanisms of different pain conditions, in order to hopefully achieve the vision of mechanism-based pain diagnoses

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Diurnal beta-endorphin changes in human cerebrospinal fluid

Cited by 26 publications

References 12 publications

Convergent, functionally independent signaling by mu and delta opioid receptors in hippocampal parvalbumin interneurons

Convergent, functionally independent signaling by mu and delta opioid receptors in hippocampal parvalbumin interneurons

Volume transmission of beta-endorphin via the cerebrospinal fluid; a review

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

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